Cell-Signaling Pathways May Be Crucial To Immunosuppressive Therapy

In yet another step forward in cell signaling research, scientists at the Paola Castagnoli research group recently discovered a signaling network located in blood-forming cells. Based on the results of the study commissioned by the A*STAR Singapore Immunology Network, cell signaling pathways may be crucial in the development of more effective immunosuppressive treatments that involve the controlling of pathways in a bid to encourage the growth of infection fighting immune cells.


The results of the study could be especially significant for patients that undergo organ transplants, or those with autoimmune conditions. These patients are at especially high risk for infections and illness, and the study suggests that this may partly be the result of drug side effects that were previously unidentified. But the farther reaching implication is that the actions of the pathway could provide a clue to the control system governing immunity.


According to Jan Fric of the Castagnoli research group, the results of the study may explain the high incidence of infection among patients undergoing immunosuppressive drug therapy. He also said however that more research is required to support the group’s findings.


The study conducted by a joint team composed of researchers in Singapore and Austria examined the action of NFAT signaling pathways in myeloid cells. ‘NFAT’ is the term for a group of proteins known as transcription factors, which adhere to DNA and control certain types of genes. NFATs are responsible for continually renewing the different blood cells that develop from progenitor cells produced by the bone marrow. NFATs are essential components of a healthy immune system, and they are also responsible for manufacturing T-cells. These cells play a crucial role in the regulation of the immune system and the elimination of diseased or infected cells.


Even more important discoveries were made in studies of the intricate cell signaling and control networks which involved live laboratory mice and cultured human cells. One of the most significant findings showed that stem cells present in the bone marrow mature into a variety of myeloid cells comprising the immune and blood systems. For Fric, these findings are crucial in bringing knowledge of immune system control one step further.


The research team also discovered the role of calcineurin in activating the NFAT transcription factor system. Calcineurin, which is a type of protein that triggered into action by calcium ions, blocks the production and development of granulocyte-monocyte progenitor or GMP cells. The researchers therefore surmised that inhibiting the actions of the NFAT pathway may effectively encourage the production of GMP cells. As these cells develop, they mature into myeloid cells that can then help the body fight off infections.


According to Fric, the calcineurin–NFAT pathway is a promising area of research and study, particularly with regard to the development of autoimmune drug treatments. For Fric, the next logical step is the continued investigation on the effect that pathway therapy have on myeloid cell development in patients with autoimmune-related conditions. Nevertheless, Fric cautions against discarding current immunosuppressive drug therapies–which are generally quite effective–until there are further findings on cell signaling research.